The objective is to understand how acetylcholine reacts with acetylcholine receptor (AChR) at the molecular level, and to explain how cholinergic drugs and cholinergic toxicants exert their action on AChR. The first steps involve extension of our work on purification, of AChR from Torpedo using affinity chromatography, electrofocusing, centrifugation and eectrophoresis. After purification, attempts will be made to reconstitute a synapse-like system using pure AChR with model membranes. We will also attempt to establish the mechanism by which acetylcholine causes in AChR the configurational changes whose existence is expected. The receptor-like macromolecules in lobster axons will be further explored, and their relation to grayanotoxin-sensitive mechanism will be studied.